Patterns of CD16 and CD56 expression in persistent expansions of CD3+NKa+ lymphocytes are predictive for clonal T-cell receptor gene rearrangements

Phenotypic characteristics, and correlations between the expression of membrane NK-associated (NKa) determinants (CD11b, CD16, CD56 and CD57) and T cell receptor (TCR) genotypic patterns, were examined in 25 patients with persistent (greater than 6 months) expansions of CD3+WT31+NKa+ (CD8+ and CD8dim+) lymphocytes. These studies showed that distinct NKa phenotypic profiles were restricted to cases with rearranged TCR configurations and that clonal CD3+NKa+ components could be predicted in most cases by assessing relationships between membrane CD16 and CD56 expression. For all normal NKa subpopulations, there was a high correlation (P less than 0.0001; n = 31) between the expression of these two membrane determinants. Markedly increased CD16 expression by CD3+NKa+ cells, in relation to CD56 (i.e. a high CD16:CD56 ratio), was found exclusively in cases with rearranged TCR (13/16 cases); 2/3 of the remaining cases showing significantly reduced CD16:CD56 ratios and high (greater than 2.0) CD3+CD56+ absolute numbers. In contrast, 7/9 of the germline TCR cases had a normal CD16:CD56 ratio and 2/9 a decreased ratio with low (less than 1.0) CD3+CD56+ absolute numbers. A high ratio of CD16:CD56 expression by CD3+NKa+ lymphocytes was therefore informative for 82% of TCR rearrangements in this series; and analysis of CD16 and CD56 expression was predictive for germline and rearranged TCR configurations in 24/25 persistent CD3+NKa+ expansions.     

Correlates of well-being in mothers of children and adolescents with cystic fibrosis

Fifty mothers and 44 well siblings of children and adolescents with cystic fibrosis (CF) participated in this study to identify correlates of maternal well-being. Participants completed postal questionnaires which assessed maternal well-being, problems experienced surrounding the illness and treatment and the nature of the sibling relationship. Due to the demanding nature of treatment and the fact that CF is both genetic and incurable at present we anticipate mothers of these children will experience higher levels of stress and consequently poorer well-being than the normal population. In addition, illness severity, problems with adherence to treatment, child communication, maternal support and the sibling relationship are expected to relate to maternal well-being. Mothers in this sample did not rate their well-being as any different to the normal population. Results suggest that mothers are likely to rate their own well-being as poor when they report more frequent problems surrounding the illness and treatment and well children rate their sibling relationship as having frequent disagreements and aggression. This study highlights factors that are related to maternal well-being in families where one child has CF. These mothers as a group do not appear to be experiencing more stress in their daily lives than the normal population but certain illness and family variables are related to their well-being when examining the mothers on certain dimensions.     

Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma.

Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.     

Graft-versus-leukemia and graft-versus-host reactions after donor lymphocyte infusion are initiated by host-type antigen-presenting cells and regulated by regulatory T cells in early and long-term chimeras.

Regulatory T (T(reg)) cells and host antigen-presenting cells (APCs) have been implicated in graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect after donor lymphocyte infusion (DLI), but their relative contributions remain unclear in early versus long-term complete donor or mixed murine allogeneic hematopoietic stem cell (HSC) chimeras. We have previously demonstrated that donor HSC-derived Thy1(+) T(reg) cells, consisting primarily of CD4(+)CD25(+) cells, play an important role in the suppression of graft-versus-host (GVH) reactivity when DLI is given to complete donor chimeras 28 days after HSC transplantation. Data presented here demonstrate that protection against GVHD exerted by Thy1(+) T(reg) cells is less evident with time and eventually is not required in long-term complete donor chimeras because of an absence of host-type APCs to activate alloreactive T cells. Lethal GVHD was observed when Thy1(+) T(reg) cells were depleted from complete donor chimeras given by DLI at day 28, 35, or 42; however, T(reg) cell depletion and DLI at day 70 no longer induced GVHD-associated mortality. Moreover, the failure of DLI to induce GVHD with T(reg) depletion correlated with a loss of the DLI-induced GVL effect in long-term (day 100) complete donor chimeras. In contrast to the results from complete donor chimeras, GVL reactivity in day 100 mixed chimeras was robust after DLI. Loss of a DLI-induced GVL effect in long-term complete donor chimeras was attributed to the absence of host APCs because the infusion of exogenous host-type dendritic cells partially restored both DLI-induced GVL and GVH reactions in day 100 complete donor chimeras. The GVL and GVH reactions restored by infusion of host dendritic cells in day 100 complete donor chimeras were at least partially regulated by T(reg) cells because transient depletion of CD25(+) cells increased both the GVL effect and the severity of GVHD after DLI. Taken together, these data suggest that T(reg) cells can regulate DLI-induced GVL and GVH reactions in both early and long-term complete donor chimeras, and a state of mixed chimerism is superior to complete donor chimerism because host-type APCs facilitate a DLI-induced GVL effect without severe GVHD.     

A multimethod assessment of behavioral and emotional adjustment in children with asthma

OBJECTIVE: Examine behavioral adjustment and emotion regulation among 6-year-old children with asthma and a group of healthy controls. METHOD: Subjects were 81 children with asthma and 22 healthy controls. Asthma and allergy statuses were confirmed by objective measures. Emotional and behavioral functioning were assessed through parent report, child interview, and child participation in an emotional regulation paradigm. RESULTS: Maternal report revealed more internalizing and total behavior problems for children with asthma compared to controls. Child interview and behavioral observations of emotion regulation yielded no differences between groups. Severity of asthma was related to increased emotional difficulties by clinician interview and observation but not by maternal report. CONCLUSIONS: Two groups of children with asthma who have psychological difficulties include those with increased anxiety and those with poor emotion regulation and more asthma symptoms. Different measures of child adjustment yield a complex picture of the behavioral difficulties associated with pediatric asthma.